Journal of Experimental Biology

Skip to main page content

•  HOME 
•  ARCHIVE 
• ABOUT US
  • About JEB
  • About COB
  • Travelling fellowships
  • Grants and funding
  • JEB symposia
  • COB workshops
  • JEB in the News
  • Special Issues
• AUTHOR INFO
  • Submit a manuscript
  • Article types
  • Editor specialities
  • Manuscript preparation
  • Figure preparation
  • Supplementary material
  • Cover suggestions
  • Outstanding paper prize
• JOURNAL INFO
  • Editorial board
  • Reviewer guidelines
  • Editorial policies
  • Access policies
  • Publishing ethics
  • Rights and permissions
  • Media policies
• SUBSCRIBE
  • General information
  • Agents
  • Individuals and societies
  • Institutions
  • Consortia
  • Contact us
• CONTACT US
  • Contact JEB
  • Feedback
• HELP

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brown, D. Articles by Marshansky, V. Search for Related Content PubMed Articles by Brown, D. Articles by Marshansky, V. Social Bookmarking                         What's this?

Regulation of the V-ATPase in kidney epithelial cells: dual role in acid–base homeostasis and vesicle trafficking

Dennis Brown^*, Teodor G. Paunescu, Sylvie Breton and Vladimir Marshansky

Center for Systems Biology, Program in Membrane Biology/Nephrology Division, Massachusetts General Hospital, Boston, MA 02114, USA and Harvard Medical School, Boston, MA 02115, USA

^* Author for correspondence (e-mail: brown.dennis{at}mgh.harvard.edu)

Accepted 26 January 2009

The proton-pumping V-ATPase is a complex, multi-subunit enzyme that is highly expressed in the plasma membranes of some epithelial cells in the kidney, including collecting duct intercalated cells. It is also located on the limiting membranes of intracellular organelles in the degradative and secretory pathways of all cells. Different isoforms of some V-ATPase subunits are involved in the targeting of the proton pump to its various intracellular locations, where it functions in transporting protons out of the cell across the plasma membrane or acidifying intracellular compartments. The former process plays a critical role in proton secretion by the kidney and regulates systemic acid–base status whereas the latter process is central to intracellular vesicle trafficking, membrane recycling and the degradative pathway in cells. We will focus our discussion on two cell types in the kidney: (1) intercalated cells, in which proton secretion is controlled by shuttling V-ATPase complexes back and forth between the plasma membrane and highly-specialized intracellular vesicles, and (2) proximal tubule cells, in which the endocytotic pathway that retrieves proteins from the glomerular ultrafiltrate requires V-ATPase-dependent acidification of post-endocytotic vesicles. The regulation of both of these activities depends upon the ability of cells to monitor the pH and/or bicarbonate content of their extracellular environment and intracellular compartments. Recent information about these pH-sensing mechanisms, which include the role of the V-ATPase itself as a pH sensor and the soluble adenylyl cyclase as a bicarbonate sensor, will be addressed in this review.

Key words: H⁺-ATPase, soluble adenylyl cyclase, intercalated cells, proton secretion, acidification, pH sensing

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				N. Da Silva, T. Pisitkun, C. Belleannee, L. R. Miller, R. Nelson, M. A. Knepper, D. Brown, and S. Breton Proteomic analysis of V-ATPase-rich cells harvested from the kidney and epididymis by fluorescence-activated cell sorting Am J Physiol Cell Physiol, June 1, 2010; 298(6): C1326 - C1342. [Abstract] [Full Text] [PDF]

				C. Belleannee, N. Da Silva, W. W. C. Shum, D. Brown, and S. Breton Role of purinergic signaling pathways in V-ATPase recruitment to apical membrane of acidifying epididymal clear cells Am J Physiol Cell Physiol, April 1, 2010; 298(4): C817 - C830. [Abstract] [Full Text] [PDF]

				T. G. Paunescu, M. Ljubojevic, L. M. Russo, C. Winter, M. M. McLaughlin, C. A. Wagner, S. Breton, and D. Brown cAMP stimulates apical V-ATPase accumulation, microvillar elongation, and proton extrusion in kidney collecting duct A-intercalated cells Am J Physiol Renal Physiol, March 1, 2010; 298(3): F643 - F654. [Abstract] [Full Text] [PDF]